title: Towards the goal of personalized medicine in gastric cancer--time to move beyond HER2 inhibition. Part I: Targeting receptor tyrosine kinase gene amplification.
abstract: Gastric cancer is the second leading cancer cause of death globally. Apart from the successful targeting of HER2 over-expression in gastric cancer (GC) with trastuzumab, other targeted therapies in GC have fallen short or still in early clinical development. While HER2 over-expression accounts for up to 20% of GC, other potential actionable driver mutations occur a much lower frequency in GC. In this review we describe some of the more interesting genetic aberrations including driver mutations in gastric cancer that have very potent inhibitors against them already in clinical development. Part I of this review will focus on the receptor tyrosine kinase (RTK) gene amplification (HER2, FGFR2, MET, EGFR). Part II will devoted to gene mutations (HER2, KRAS, PIK3CA, BRAF) and gene rearrangement (ROS1, BRAF, HER2). Because of the low frequency of these potential driver mutations, perseverance in screening for these mutations will be needed in order to enroll enough of each uniquely molecularly defined subset of GC in order to demonstrate significant clinical benefit in a unique molecularly targeted therapy trial. This approach has been successfully employed in the clinical approval of crizotinib for the treatment of ALK-rearranged non-small cell lung cancer.
authors.affiliation: Department of Hematology and Oncology, Samsung Medical Center, SungKyunKwan University School of Medicine, Seoul, 135-710, South Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Sai-Hong Ignatius
authors.initials: SH
authors.lastname: Ou
mesh_terms: D005784:Gene Amplification; D006801:Humans; D058990:Molecular Targeted Therapy; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*
chemical_list: D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human